The analysis for molecular mechanism of lifespan regulation by RNA binding protein

• Project/Area Number: 25670138
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: AKIYAMA Tetsu 東京大学, 分子細胞生物学研究所, 教授 (70150745)
• Project Period (FY): 2013-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: 寿命 / 老化 / 脂肪組織 / 分化

Outline of Final Research Achievements

Mex-3B is an RNA-binding protein, but its function is poorly understood, We found that Mex-3B-deficient mice are long-lived. We therefore attempted to elucidate the molecular mechanisms underlying lifespan regulation by Mex-3B.We found that Mex-3B deficient mice were resistant to obesity and showed significantly decreased adipocyte tissue weights. In addition, we found that Mex-3B were down-regulated in adipocyte tissues by caloric restriction, a well-known method to extend lifespan. These results suggest that Mex-3B regulates lipid metabolism in adipocyte tissues, and Mex-3B deficiency prolongs lifespan by a mechanism similar to that involved in lifespan extension by caloric restriction.
We also performed adipocyte differentiation assays using Mex-3B-deficient cells. We found that Mex-3B deficiency suppressed adipocyte differentiation. Thus, lifespan extension and resistance to obesity seen in Mex-3B-deficient mice may be resulted from suppression of adipocyte differentiation.

Research Products

• [Journal Article] The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumourigenesis. (2014)
  • Author(s): Tsuji S
  • Journal Title: Nature Communications Volume: 5 Pages: 3150-3150
  • DOI: 10.1038/ncomms4150
  • Peer Reviewed / Open Access
• [Journal Article] PCDH10 is required for the tumorigenicity of glioblastoma cells. (2014)
  • Author(s): Kanae Echizen, Mitsutoshi Nakada , Tomoatsu Hayashi, Hemragul Sabit, Takuya Furuta, Miyuki Nakai, Ryo Koyama-Nasu, Yukiko Nishimura, Kenzui Taniue, Yasuyuki Morishita, Shinji Hirano, Kenta Terai, Tomoki Todo, Yasushi Ino, Akitake Mukasa, Shunsaku Takayanagi, Ryohei Ohtani, Nobuhito Saito, Tetsu Akiyama
  • Journal Title: Biochem Biophys Res Commun. Volume: 444 Pages: 13-18
  • DOI: 10.1016/j.bbrc.2013.12.138
  • Peer Reviewed / Open Access
• [Journal Article] The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells. (2014)
  • Author(s): Koyama-Nasu R, Haruta R, Nasu-Nishimura Y, Taniue K, Katou Y, Shirahige K, Todo T, Ino Y, Mukasa A, Saito N, Matsui M, Takahashi R, Hoshino-Okubo A, Sugano H, Manabe E, Funato K & Akiyama T
  • Journal Title: Oncogene Volume: 33 Pages: 2236-2244
  • DOI: 10.1038/onc.2013.168
  • Peer Reviewed / Open Access
• [Journal Article] Riccardo Fodde, Takao Senda. Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia (2014)
  • Author(s): Takanori Onouchi, Katsunori Kobayashi, Kazuyoshi Sakai, Atsushi Shimomura, Ron Smits, Chiho Sumi-Ichinose, Masafumi Kurosumi Keizo Takao, Ryuji Nomura, Akiko Iizuka-Kogo, Hidenori Suzuki,Kazunao Kondo, Tetsu Akiyama Tsuyoshi Miyakawa Riccardo Fodde and Takao Senda, Riccardo Fodde, Takao
  • Journal Title: Mol Brain Volume: 7 Pages: 1-14
  • DOI: 10.1186/1756-6606-7-21
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] he miR-1-NOTCH3-Asef pathway is important for colorectal tumor cell migration (2013)
  • Author(s): Shiori Furukawa,Yoshihiro Kawasaki, Masaya Miyamoto, Masaya Hiyoshi,Joji Kitayama, Tetsu Akiyama
  • Journal Title: PLoS One Volume: 8
  • DOI: 10.1371/journal.pone.0080609
  • Peer Reviewed / Open Access
• [Journal Article] Differences in the localization of the APC-Asef/Asef2 complex between APC wild-type and mutant cells (2013)
  • Author(s): Yoshihiro Kawasaki, Shiori Furukawa, Rina Sato, Tetsu Akiyama
  • Journal Title: Cancer Science Volume: 8 Pages: 1135-1138
  • DOI: 10.1111/cas.12180
  • Peer Reviewed
• [Journal Article] The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells. (2013)
  • Author(s): R Koyama-Nasu, Y Nasu-Nishimura, T Todo, Y Ino, N Saito, H Aburatani, K Funato, K Echizen, H Sugano, R Haruta, M Matsui, R Takahashi, E Manabe, T Oda and T Akiyama
  • Journal Title: Oncogene Volume: 32 Pages: 3840-3845
  • DOI: 10.1038/onc.2012.399
  • Peer Reviewed
• [Journal Article] Crystal structure of the guanylate kinase domain from Discs large homolog 1 (DLG1/SAP97). (2013)
  • Author(s): Shinji Mori, Yuta Tezuka, Akihiko Arakawa, Noriko Handa, Mikako Shirouzu, Tetsu Akiyama, Shigeyuki Yokoyama
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 435 Pages: 334-338
  • DOI: 10.1016/j.bbrc.2013.04.056
  • Peer Reviewed
• [Journal Article] Alendronate attenuates eosinophilic airway inflammation associated with suppression of Th2 cytokines, Th17 cytokines, and eotaxin-2 (2013)
  • Author(s): Oh Sasaki, Mitsuru Imamura, Yusuke Yamazumi, Hiroaki Harada, Taku Matsumoto, Katsuhide Okunishi, Kazuyuki Nakagome, Ryoichi Tanaka, Tetsu Akiyama, Kazuhiko Yamamoto and Makoto Dohi
  • Journal Title: Journal of Immunology Volume: 191 Pages: 2879-2889
  • DOI: 10.4049/jimmunol.1300460
  • Peer Reviewed
• [Journal Article] Novel mouse model for Gardner syndrome generated by a large-scale ENU mutagenesis program. (2013)
  • Author(s): Toki H, Inoue M, Motegi H, Minowa O, Kanda H, Yamamoto N, Ikeda A, Karashima Y, Matsui J, Kaneda H, Miura I, Suzuki T, Wakana S, Masuya H, Gondo Y, Shiroishi T, Akiyama T, Yao R, Noda T
  • Journal Title: Cancer Sci. Volume: PMID: 23551873 Pages: 937-44
  • DOI: 10.1111/cas.12161
  • Peer Reviewed
• [Journal Article] Decreased Apoptosis and Persistence of the Common Nephric Duct During the De-velopment of an Aberrant Vesicoureteral Junction in Dlg1 Gene-Targeted Mice (2013)
  • Author(s): Akiko Iizuka-Kogo, Tetsu Akiyama, Takao Senda
  • Journal Title: The Anatomical Record Volume: 296 Pages: 1936-1942
  • DOI: 10.1002/ar.22814
  • Peer Reviewed
• [Presentation] ”Long non-coding RNA ASBEL required for tumorigenicity of colon cancer (2014)
  • Author(s): Kenzui Taniue, Tetsu Akiyama
  • Organizer: Long Noncoding RNAs: Marching toward Mechanism
  • Place of Presentation: Santa Fe, New Mexico, USA
  • Year and Date: 2014-02-27 – 2014-03-04
• [Presentation] ASBEL, an ANA/BTG3 antisense transcript required for tumorigenicity of ovarian carcinoma. (2013)
  • Author(s): 谷上 賢瑞、秋山 徹
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-10-03 – 2013-10-05
• [Presentation] RNA結合タンパク質D8はc-junの転写後制御を介してAPC (Min/+)マウスにおける腫瘍形成を制御する (2013)
  • Author(s): 山角 祐介、渡邊 紘介、小田 健昭、佐藤 裕美、秋山 徹
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-10-03 – 2013-10-05
• [Presentation] 神経膠芽腫の発症における5-hydroxymethylcytosineの役割 / Role of 5-hydroxymethylcytosine in the tumorigenicity of glioblastoma cells (2013)
  • Author(s): 高井 弘基、秋山 徹
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-10-03 – 2013-10-05
• [Presentation] The role of miR-363-GATA6-Lgr5 pathway in colorectal tumorigenesis (2013)
  • Author(s): 川崎 善博、辻 真之介、古川 史織、谷上 賢瑞、林 寛敦、日吉 雅也 、北山 丈二 、秋山 徹
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-10-03 – 2013-10-05
• [Presentation] Functional analysis of a novel long ncRNA involved in the tumorigenicity of colorectal cancer. (2013)
  • Author(s): Kenzui Taniue,Akiko Kurimoto,Hironobu Sugimasa, Emiko Nasu, Takeshi Nagashima,Mariko Okada-Hatakeyama,Tetsu Akiyama
  • Organizer: AACR
  • Place of Presentation: ワシントンDC
  • Year and Date: 2013-04-06 – 2013-04-10
• [Patent(Industrial Property Rights)] 延寿命制御活性を有する物質をスクリーニングする方法 (2013)
  • Inventor(s): 秋山徹 他3名
  • Industrial Property Rights Holder: 秋山徹 他3名
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-07-24
  • Application Year: 2013